Bloody battle of the sexes: Male and female plasma have different protein profiles

Transfusion risks with plasma

Blood transfusions are carried out so routinely by the medical profession around the world that you would be forgiven for thinking that they are completely safe. But think again. Patients who receive certain blood products, especially those containing plasma, are at risk from transfusion related acute lung injury (TRALI), a serious pulmonary syndrome that can lead to death if not caught early.

TRALI is a severe acute reaction characterised by respiratory distress, hypoxia and pulmonary infiltrates soon after transfusion. It has no apparent cause and the true incidence is unknown. This condition has been reported to occur after the transfusion of all types of blood components but the risks from platelets and fresh frozen plasma appear to be higher. With prompt support, clinical improvement is generally observed within 48-96 hours, with oxygen provided through a mask or some form of ventilation.

In recent years, the incidence of TRALI has seen a reduction due to the use of male-only plasma, with far fewer deaths reported. So, it appears that there are differences between male and female plasma that affect the patient upon transfusion. A team of scientists based in the US postulated that there might be a disparity in the coagulation factors and other proteins between the genders so set about comparing the proteomes of male and female plasma in the first study of its type.

Plasma protein profiles

Christopher Silliman from the Bonfils Blood Center, Denver, CO, worked with colleagues from the University of Colorado Denver, Aurora, Denver Health Medical Center and the South Texas Blood and Tissue Center, San Antonio, and published their findings in Transfusion.

Plasma was collected under US FDA guidelines from five healthy men all with blood group A+ and five healthy, non-pregnant women with blood groups O+ (3) and A+ (2). The 14 most abundant plasma proteins were removed from each sample using a commercial affinity spin cartridge and the proteins remaining were separated by 1D gel electrophoresis.

Each lane on the gel was cut into pieces and the proteins present were enzymatically digested for conventional analysis by LC/MS using electrospray ionisation. The proteins were identified from their tandem mass spectra by matching with the human protein database.

A total of 231 proteins were identified and there were some significant differences in their abundances between genders, as estimated by a spectral counting method. Some of the differences were supported by standard biochemical assays for particular proteins.

Gender differences in plasma revealed

One of the expected differences was the vast superiority of the pregnancy zone protein in females over males, because this protein is directly related to the hormones that are responsible for gender differences. But the other protein abundance changes were totally unexpected.

Female plasma contained twice as much coagulation factor FV, alpha1-antitrypsin and beta2-microglobulin as male plasma and 1.5-2-fold more of complement factors H and C4B.

Conversely, male plasma had 2-fold more protein Z-dependent protease inhibitor and Fc binding protein, 3-fold more protein S100, 4-fold more phosphatidylinositol glycan-specific phospholipase and 14-fold more transgelin-2.

As well as being unexpected, the differences could not be explained, says Silliman. The small sample size of 10 people might be a factor and he recognises that a far greater number of plasma samples need to be tested to confirm the conclusions.

In addition, only three blood groups were represented by the volunteers. However, it has been shown previously that none of these raised proteins differed between ABO or Rh blood groups, or between A+ and O+ females, so blood type is less likely to be a factor in this work.

If these conclusions are corroborated by more work, it might suggest that male or female plasma could be selectively transfused to patients, depending on their condition. For instance, female plasma, with its higher load of coagulation factor FV, might give a better outcome in cases of acute organ injury and multiple organ failure. Conversely, male plasma has already been shown to reduce the incidence of TRALI.

But "these advantages are theoretical and would require careful outcome analyses in well-matched patient cohorts before any definitive statement could be made," says Silliman.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.